紫杉醇联合顺铂通过Wnt/β-catenin信号通路抑制鼻咽癌肿瘤干细胞增殖并促进其凋亡  

Paclitaxel and cisplatin inhibit the proliferation of nasopharyngeal cancer stem cells and promote apoptosis via the Wnt/beta-catenin pathway

作　　者：刘永刚[1] 杨荣松[1] 吴红方[2] 张保朝[3] 

机构地区：[1]南阳市中心医院耳鼻喉科,河南省南阳市473000 [2]南阳市中心医院病理科,河南省南阳市473000 [3]南阳市中心医院神经内科,河南省南阳市473000

出　　处：《中国组织工程研究》2016年第41期6118-6124,共7页Chinese Journal of Tissue Engineering Research

基　　金：河南省医学科技攻关计划项目(201403227)~~

摘　　要：背景:肿瘤干细胞具有自我更新和分化成新肿瘤的能力,会导致肿瘤放化疗不敏感,是肿瘤发生和复发的根源。目的:探索紫杉醇联合顺铂对鼻咽癌干细胞增殖和凋亡的影响并探索其作用的信号通路。方法:免疫磁珠的方法分离培养鼻咽癌干细胞,紫杉醇和顺铂处理细胞,Western blot检测凋亡相关蛋白caspase-3、活化的caspase-3、Bcl-2和β-catenin及下游原癌基因c-myc的表达,用RNA干扰技术敲降β-catenin表达或者使用抑制剂XAV939抑制Wnt/β-catenin通路活性,MTT法检测细胞增殖率,流式细胞仪检测细胞凋亡。结果与结论:(1)紫杉醇或顺铂均会抑制鼻咽癌干细胞的增殖,促进其凋亡,并且凋亡标志蛋白活化caspase-3表达上升,凋亡抑制蛋白Bcl-2表达下降,联合用药具有协同作用,(2)紫杉醇或顺铂均会抑制Wnt/β-catenin通路的活性及下游靶基因c-myc的表达,抑制Wnt/β-catenin通路活性抑制鼻咽癌干细胞的增殖,促进其凋亡。(3)结果表明,紫杉醇和顺铂可能是通过Wnt/β-catenin信号通路调控鼻咽癌干细胞的增殖和凋亡。BACKGROUND： Cancer stem cells have self-renewal ability and can differentiate into new tumors. Cancer stem cells are the source of tumor formation and recurrence, and they can make tumors insensitive to radiotherapy and chemotherapy. OBJECTIVE： To explore the effect of paclitaxel plus cisplatin on the proliferation and apoptosis of nasopharyngeal cancer stem cells（NPCSCs） and involved signal pathways. METHODS： NPCSCs were sorted by immunomagneticbeads and were treated with paclitaxel, cisplatin or their combination. The expression of caspase-3, activated caspase-3 and Bcl-2, which are related to apoptosis, was determined by western blot. The expression of β-catenin and its downstream proto-oncogene, c-myc, was also determined by western blot. The activity of the Wnt/β-catenin pathway was inhibited by knocking down β-catenin expression or β-catenin inhibitor XAV939. Proliferation and apoptosis of NPCSCs were detected by MTT and flow cytometry, respectively. RESULTS AND CONCLUSION： Either paclitaxel or cisplatin could inhibit proliferation and induce apoptosis of NPCSCs. The expression of apoptosis marker, activated caspase-3, was increased and the expression of the inhibitor of apoptosis, Bcl-2, was declined. Combined use of paclitaxel and cisplatin had synergistic effect when used together. Either paclitaxel or cisplatin could inhibit the expression of β-catenin and c-myc, suppressed the proliferation and induced the apoptosis of NPCSCs by inhibiting the activity of Wnt/β-catenin pathway. These results indicate that the combined use of paclitaxel and cisplatin may inhibit the proliferation of NPCSCs and promote apoptosis via the Wnt/β-catenin pathway.

关 键 词：干细胞 肿瘤干细胞 紫杉醇 顺铂 鼻咽癌干细胞 WNT/Β-CATENIN通路 增殖 凋亡 

分 类 号：R318[医药卫生—生物医学工程]